A Mass Spectrometry Research Resource at Pacific Northwest National Laboratory for the development and application of advanced instrumental methods in support of biomedical research is described. The facility's Core technological research efforts will involve the development of instrumental methods based upon electrospray ionization (ESI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry for the ultra-sensitive characterization of biopolymers. The extremely high resolution and accurate mass measurements feasible with FTICR for larger biopolymers allows more effective identification and provides more extensive structural information. The Resource will utilize nano-scale separation capabilities based upon capillary electrophoresis and micro-fabricated devices for the manipulation of very small samples. In combination with other Core efforts that will improve the overall sensitivity and quality of FTICR, the Resource will enable measurements that are orders of magnitude more sensitive than feasible with conventional instrumentation. These capabilities will be used, for example, for global measurements of proteomes that circumvent the limitations of present 2-D gel technology, and allow rapid studies of protein expression in complex systems with far greater sensitivity than currently possible. The Resource will exploit new instrumentation already available, including a high-magnetic-field (11.5 tesla) FTICR having two complete spectrometers, as well as 3.5 and 7 tesla FTICRs and other mass spectrometric instrumentation. The Resource will leverage a large investment by DOE, as well substantial on-going support that includes equipment maintenance and a unique "collaboratory" research environment. The Resource will serve to make its advanced capabilities available to regional and national collaborators and users in biological research. Important biomedical collaborative efforts will include uniquely informative measurements of neurochemical processes at the single cell level, studies of large protein-protein and protein-DNA interactions not effectively studied with other methods, and the identification of phosphoproteins and their differential state of phosphorylation in T cells committed to a proliferating or anergic state in response to altered peptide ligands.